The relationship between the development of tolerance and physical dependence to tetrahydrocannabinol (THC) and marijuana self-administration by smoking will be determined. Changes in levels of drug self-administration have rarely been studied in situations where level of tolerance or abstinence is independently manipulated by the experimenter. Marijuana has characteristics that make it ideal to test determinants of drug self-administration that may be applicable to many drugs. The experiments should also provide useful new information specific to marijuana . Twenty experienced marijuana smokers living on a research ward for 25 days will be given repeated doses of oral THC at doses to produce two levels of tolerance (10 mg and 20 mg doses). In previous experiments the higher dose level was reliably followed by an abstinence syndrome after eight days intoxication. During periods of placebo and oral THC administration, subjects will be allowed free access to marijuana cigarettes with amount smoked and physioligic and psychologic effects carefully measured. Measures of smoking behavior include puff volume and inhalation depth measures and repeated measures of cardiovascular, EEG and symptom and behavior changes. Plasma THC and THC metabolite levels will be meausred. Changes in marijuana smoking, dose absorbed and effects will be followed through cycles of acquired tolerance and withdrawal over a 25 day period. Methods involve disciplines of psychopharmacology, psychophysiology, pharmacokinetics and behavioral medicine. Health implications include a better understanding of determinants and consequences of drug self-administration, particularly marijuana administration.